Evaluation of drug candidates for Chagas Disease

• Grant number: 24/18196-3
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: May 05, 2025
• End date: June 24, 2025
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Adriano Defini Andricopulo
• Grantee: Jackson Vieira Leitão
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Chagas disease is a neglected tropical disease that affects between 6 and 7 million people and is considered a global health problem due to the migratory flow of infected individuals. The highest incidences of Chagas disease are recorded in Latin America, where it is estimated that approximately 75 million people are at risk of contracting the disease worldwide. Additionally, over 10,000 people die annually due to complications associated with the disease. One of the main factors contributing to this high number of deaths is the lack of proper diagnosis and treatment, with only 1% of infected individuals receiving appropriate care. Moreover, the two available drugs for the treatment of Chagas disease have low efficacy and safety concerns. In this context, the development of new drugs that target specific biochemical pathways in the parasites is urgently needed to achieve greater selectivity and minimize the adverse effects characteristic of current therapies. The research project aims to evaluate drug candidates for the treatment of Chagas disease through the use of experimental and computational methods applied to drug design. To this end, the biological activity of a series of previously synthesized compounds will be evaluated against the intracellular form of Trypanosoma cruzi amastigotes. Tests in human cell cultures will be conducted to assess the toxicity and selectivity of the compounds, using fibroblast (HFF-1) and hepatocyte (HepG2) cell lines. In silico and in vitro pharmacokinetic studies will be performed to analyze properties such as permeability, metabolism, and distribution coefficient (eLogD). The data generated will be used for molecular property modeling, which will guide the design of new compounds. The project will be developed at the Laboratory of Medicinal and Computational Chemistry (LQMC) at the Institute of Physics of São Carlos (IFSC-USP) under the supervision of Prof. Adriano Defini Andricopulo and will contribute to the development of new therapies for endemic diseases in Brazil. (AU)